A pilot study on the role of the oxytocinergic system in gut microbiome composition in children with autism: baseline associations and effects of intranasal oxytocin

Autistic children often experience behavioral difficulties alongside nutritional and gastro-intestinal (GI) problems, including gut dysbiosis. Recent research has highlighted important interactions between the oxytocinergic system and gut microbiome compositions, however, insights into how exogenous administration of oxytocin may influence GI health remain largely unexplored. Here, we first examined whether nutrition, GI symptoms and microbiome compositions vary in autistic versus non-autistic children, and how alterations link to clinical-behavioral difficulties and oxytocinergic signaling. Next, we examined the effect of a four-week intranasal oxytocin administration regimen on GI health/dysbiosis in autistic children enrolled in a randomized placebo-controlled trial. Compared to non-autistic children, autistic children consumed more soft drinks, and fewer vegetables and experienced abdominal pain more frequently over the past three months. Notably, epigenetic variations in the oxytocin receptor gene (OXTR) were associated with stool consistency, indicating that children with looser stools exhibited lower OXTR methylation levels, indicative of increased receptor expression. Additionally, a higher abundance of Romboutsia was associated with OXTR hypo-methylation and more anxiety-like behavior. In autistic children, the four-week oxytocin regimen had no effect on bacterial diversity but did modify stool consistency, leading to less dense stools with an overall more normal stool consistency, and an increased abundance of the potentially anti-inflammatory genus Fusicatenibacter. To conclude, this study provides novel insights into the role of the oxytocinergic system in GI symptoms and gut microbiome compositions in autistic children, and preliminary evidence suggesting a modulatory effect of exogenously administered oxytocin on these parameters.